Gene signatures of SARS-CoV/SARS-CoV-2-infected ferret lungs in short- and long-term models

• Published in: Infection, genetics and evolution Vol. 85; p. 104438
• Main Authors: Liu, Hsin-Liang, Yeh, I-Jeng, Phan, Nam Nhut, Wu, Yen-Hung, Yen, Meng-Chi, Hung, Jui-Hsiang, Chiao, Chung-Chieh, Chen, Chien-Fu, Sun, Zhengda, Jiang, Jia-Zhen, Hsu, Hui-Ping, Wang, Chih-Yang, Lai, Ming-Derg
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2020
• Subjects: Animals; Bioinformatics; Computational Biology - methods; Coronavirus; COVID-19 - genetics; COVID-19 - metabolism; COVID-19 - virology; Disease Models, Animal; Disease Progression; Ferret (Mustela putorius furo); Ferrets; Gene Expression Profiling - methods; Gene Expression Regulation; Gene Ontology; Gene Regulatory Networks; Lung - virology; Reactive Oxygen Species - metabolism; Research Paper; SARS-CoV; SARS-CoV-2; SARS-CoV-2 - pathogenicity; Ferret (Mustela putorius furo); SARS-CoV-2; Coronavirus; Bioinformatics; SARS-CoV
• ISSN: 1567-1348; 1567-7257
• DOI: 10.1016/j.meegid.2020.104438

Coronaviruses (CoVs) consist of six strains, and the severe acute respiratory syndrome coronavirus (SARS-CoV), newly found coronavirus (SARS-CoV-2) has rapidly spread leading to a global outbreak. The ferret (Mustela putorius furo) serves as a useful animal model for studying SARS-CoV/SARS-CoV-2 infection and developing therapeutic strategies. A holistic approach for distinguishing differences in gene signatures during disease progression is lacking. The present study discovered gene expression profiles of short-term (3 days) and long-term (14 days) ferret models after SARS-CoV/SARS-CoV-2 infection using a bioinformatics approach. Through Gene Ontology (GO) and MetaCore analyses, we found that the development of stemness signaling was related to short-term SARS-CoV/SARS-CoV-2 infection. In contrast, pathways involving extracellular matrix and immune responses were associated with long-term SARS-CoV/SARS-CoV-2 infection. Some highly expressed genes in both short- and long-term models played a crucial role in the progression of SARS-CoV/SARS-CoV-2 infection, including DPP4, BMP2, NFIA, AXIN2, DAAM1, ZNF608, ME1, MGLL, LGR4, ABHD6, and ACADM. Meanwhile, we revealed that metabolic, glucocorticoid, and reactive oxygen species-associated networks were enriched in both short- and long-term infection models. The present study showed alterations in gene expressions from short-term to long-term SARS-CoV/SARS-CoV-2 infection. The current result provides an explanation of the pathophysiology for post-infectious sequelae and potential targets for treatment. •The development of Wnt and stemness signaling were related to short-term SARS-CoV/SARS-CoV-2 infection.•The extracellular matrix and immune response were associated with long-term SARS-CoV/SARS-CoV-2 infection.•Metabolic, glucocorticoid, and reactive oxygen species-associated networks were enriched in both short- and long-term SARS-CoV/SARS-CoV-2 infected models.